Acute vs. Delayed Iron Therapy: Effect on Iron Status, Anemia and Cognition

Tracking Information
First Submitted Date ICMJE	March 24, 2010
First Posted Date ICMJE	March 26, 2010
Last Update Posted Date	June 1, 2015
Study Start Date ICMJE	June 2010
Actual Primary Completion Date	December 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: March 24, 2010)	Hemoglobin change, anemia prevalence, and socioemotional behavior in the immediate iron vs. delayed iron groups [ Time Frame: 6 months ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01093989 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Acute vs. Delayed Iron Therapy: Effect on Iron Status, Anemia and Cognition
Official Title ICMJE	Acute vs. Delayed Iron Therapy: Effect on Iron Status, Anemia and Cognition
Brief Summary	The research questions to be answered by this study are: Is treatment with iron more effective at improving anemia if given at the time of a malaria episode or 1 month after the episode?; Which treatment timing is associated with more malaria episodes - 1 month delayed treatment or immediate treatment at the time of malaria?; Does timing of iron treatment affect later thinking processes and behavior?
Detailed Description	The study population in this study will be children who are enrolled in our ongoing study of cerebral malaria and severe malarial anemia, "Pathogenesis of cognitive/neurologic deficits in central nervous system malaria", underway in Kampala, Uganda. The pathogenesis study seeks to address the question of why children with severe malaria have later problems in thinking. The study we are now proposing will build on this study by assessing whether children with severe malaria have iron deficiency, and if they do, whether treatment with iron at the time of malaria is less effective than treatment one month later. We believe that treatment one month later may be more effective because there is data that shows that the inflammation that occurs with a malaria episode may decrease the body's ability to absorb iron in the gut and to send iron to the places it is needed, like the bone marrow and the brain. We are doing this study to see if our hypothesis about more effective iron treatment if it is delayed is correct and assessing anemia prevalence, iron status, and long-term neurobehavioral development as outcomes. We have three study groups: children with cerebral malaria, children with severe malarial anemia, and healthy community control children. Children found to be iron deficient will be randomized to receive iron (as ferrous sulphate syrup) either immediately or at their one-month follow-up visit. At 1-, 6, and 12-month follow-up visits changes in iron and inflammation indicators will be assessed. At the 6- and 12-month visits, neurocognitive behavior will also be evaluated and compared between the immediate vs. delayed iron groups. Malaria morbidity will be assessed via home visits during the period of iron supplementation and via clinic monitoring for the duration of the study.
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label)
Condition ICMJE	Anemia; Inflammation; Malaria Morbidity; Cognitive Development
Intervention ICMJE	Dietary Supplement: Ferrous Sulphate Syrup; Iron therapy will consist of a three-month course of ferrous sulphate syrup. For children with Hb ≥ 7 g/dL, each daily dose will be based on 2 mg iron/kg body weight.
Study Arms	Placebo Comparator: Immediate iron Iron-deficient children will be randomized to receive iron concurrently with anti-malarial treatment or one month later (delayed iron group). Intervention: Dietary Supplement: Ferrous Sulphate Syrup; Active Comparator: Delayed iron Intervention: Dietary Supplement: Ferrous Sulphate Syrup
Publications *	Cusick SE, Opoka RO, Ssemata AS, Georgieff MK, John CC. Comparison of iron status 28 d after provision of antimalarial treatment with iron therapy compared with antimalarial treatment alone in Ugandan children with severe malaria. Am J Clin Nutr. 2016 Mar;103(3):919-25. doi: 10.3945/ajcn.115.117820. Epub 2016 Feb 3.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: May 28, 2015)	239
Original Estimated Enrollment ICMJE; (submitted: March 24, 2010)	300
Actual Study Completion Date	December 2014
Actual Primary Completion Date	December 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: All children must Be between the ages of 18 mo and 5 y Reside within 20 km of study hospital; Children with cerebral malaria must have Coma (BCS < 3) P. falciparum on blood smear No clinical evidence or other causes of encephalopathy; Children with severe malarial anemia must have Hemoglobin < 5 g/dL Clinical symptoms of malaria P. falciparum on blood smear; Community control children must Live in same neighborhood or extended household as a child with severe malaria Be within one year of age as a child with severe malaria Exclusion Criteria: Cerebral malaria WBC > 10 Positive gram stain or culture Severe malarial anemia; Impaired conscious on physical exam; Seizure activity prior to or during physical exam; Any other evidence of CNS disease; All exclusion criteria of CM except no lumbar puncture required Community control children; All exclusion criteria for CM; Any active illness, recent illness, or recovery from illness; Chronic illness requiring medical care; Medical abnormalities on screening history of physical exam; CC control with a positive malaria smear will be treated but will not be excluded from the study.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Months to 5 Years (Child)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Uganda
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01093989
Other Study ID Numbers ICMJE	0909M72852; 1U01HD064698-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	University of Minnesota - Clinical and Translational Science Institute
Study Sponsor ICMJE	University of Minnesota - Clinical and Translational Science Institute
Collaborators ICMJE	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators ICMJE	Principal Investigator: Chandy C John, M.D. University of Minnesota - Clinical and Translational Science Institute
PRS Account	University of Minnesota - Clinical and Translational Science Institute
Verification Date	May 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP